{PDOC51728}
{PS51728; RTT109_HAT}
{BEGIN}
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* Rtt109-type histone acetyltransferase (HAT) domain profile *
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Histone acetyltransferase (HAT) enzymes play important roles in the regulation
of chromatin  assembly,  RNA transcription, DNA repair and other DNA-templated
reactions through  the  lysine  side-chain  acetylation  of histones and other
transcription factors.  HATs  fall into at least four different families based
on sequence  conservation  within the HAT domain. This includes Gcn5/PCAF (see
<PDOC51186>), CBP/p300,  Rtt109  and MYST families. The different HAT families
contain a  structurally  conserved  central  region  associated  with  acetyl-
Coenzyme A  (Ac-CoA)  cofactor  binding  but distinct catalytic mechanisms and
structurally divergent  flanking  regions  that  mediate  different  chromatin
regulatory functions.  Protein  acetylation  extends  beyond histones to other
nuclear proteins  and even cytoplasmic proteins to regulate diverse biological
processes including  the  regulation  of  cell  cycle,  vesicular trafficking,
cytoskeleton reorganization and metabolism.

Rtt109, also  known  as KAT11, is a recently characterized fungal-specific HAT
that modifies  histone  H3  lysine  56 (H3K56) to promote genome stability and
resistance to  a variety of DNA-damaging agents. Rtt109 does not show sequence
conservation with  other  known HATs and depends on association with either of
two histone chaperones, Asf1 or Vps75, for HAT activity [1,2,3].

The Rtt109-type  HAT  domain consists of a core HAT subdomain, which binds the
acetyl-CoA cofactor.  A second subdomain, the activation subdomain, is tightly
associated with  the  HAT  subdomain.  Autoacetylation  of a lysine within the
activation subdomain  is  required for stabilizing the interaction between the
two subdomains  and  is  essential  for  catalysis. The Rtt109-type HAT domain
contains eight  beta  strands and nine alpha helices and displays mixed three-
layered alpha/beta  architecture  with  eight  beta strands sandwiched by five
alpha helices  (alpha1-alpha5)  from one side, and four alpha helices (alpha6-
alpha9) from the other side (see<PDB:2RIM>) [1,2,3].

The profile we developed covers the entire Rtt109-type HAT domain.

-Sequences known to belong to this class detected by the profile: ALL.
-Other sequence(s) detected in Swiss-Prot: NONE.
-Last update: July 2014 / First entry.

[ 1] Lin C., Yuan Y.A.
     "Structural insights into histone H3 lysine 56 acetylation by
     Rtt109."
     Structure 16:1503-1510(2008).
     PubMed=18707894; DOI=10.1016/j.str.2008.07.006
[ 2] Tang Y., Holbert M.A., Wurtele H., Meeth K., Rocha W., Gharib M.,
     Jiang E., Thibault P., Verreault A., Cole P.A., Marmorstein R.
     "Fungal Rtt109 histone acetyltransferase is an unexpected structural
     homolog of metazoan p300/CBP."
     Nat. Struct. Mol. Biol. 15:738-745(2008).
     PubMed=18568037; DOI=10.1038/nsmb.1448
[ 3] Stavropoulos P., Nagy V., Blobel G., Hoelz A.
     "Molecular basis for the autoregulation of the protein acetyl
     transferase Rtt109."
     Proc. Natl. Acad. Sci. U.S.A. 105:12236-12241(2008).
     PubMed=18719104; DOI=10.1073/pnas.0805813105

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